Friday, July 29, 2011

Great article on the Nesiritide debacle

There has been some great articles regarding the expensive, waste of a decade induced by nesiritide.

I like this article the most because it's written by someone who is not in medicine. It tackles many of the same issues I looked at in my post, The problems with numbers, namely when drugs are approved based on intermediate end-points bad things can happen.

The best thing we can say about niseritide is that when the definitive trial was finally done, the previous concerns about renal failure, were shown to be merely illusions created by the smoke and mirrors of meta-analysis.

Acute renal failure was an early concern regarding Nesiritide...

...but when the right placebo controlled trial was done, no renal failure.
So go and read Carolyn Thomas' view of nesiritide and see how we have failed the people we are entrusted to care for.

Wednesday, July 27, 2011

Davita: is the vial half empty or half full

Early Tuesday, I caught half a headline about drugs being wasted at the expense of Medicare and to the benefit of some dialysis company. A few hours later I saw the first caustic tweets:

Just some of the angry tweets
Then I started getting direct messages asking for my thoughts. Recently, Davita has been getting more than its share of bad press recently and this seemed like more of the same. The facts of the news story, as far as I can tell, are as follows
  • A former medical director and nurse brought a whistle blower suit against Davita
  • They accuse Davita of using large vials to administer IV drugs during dialysis. The large vials resulted in excess medication being wasted
  • Medicare pays for the entire vial regardless of how much is wasted
  • The Justice department investigated this claim for more than two years and decided not to join the lawsuit
My first reaction was Davita had done a bad, bad deed here but the more I thought about it, the more that seemed to be a rush to judgment. The fact that the Justice Department, after investigating  for two years, did not join the lawsuit became the itch I could not ignore. My interpretation, is that the Feds looked into how Davita was handling the drugs and they did not find any unlawful activity.

So I was satisfied with the assumption that the way Davita was handling the drugs was legal. However, even when things are within the letter of the law we want our medical institutions to use resources efficiently. Clearly, intensionally pouring drugs down the biohazard drain, as the whistle blowers contend, is not the most efficient use of medical resources. The problem was the Medicare reimbursement system. For years, Medicare underpaid for the dialysis procedure so that dialysis providers had to turn themselves into high-end retail pharmacies that peddled Epo, and Zemplar in order to keep the lights on. With this type of system the providers were incentivized to use as much drug as possible. This perversion of fee-for-service has been at the root of almost all of the recent scandals in dialysis units. The recent anemia controversies were driven to the forefront largely because dialysis companies were payed for giving drugs not for patient oriented outcomes.

Its clear to me that retail pharmacy system was not the system we wanted. The laws need to change and you know what? This system is no longer the law. Bundling began earlier this year and removes these perverted incentives in order to better align provider and patient goals. In response to the new incentives you know what happened? The vials became right sized and Epo use plummeted. It's too early to see how bundling effects patient outcomes but Davita and the other Large Dialysis Organizations are responding to the new incentives.

The lesson here is that incentives drive medical decision making. Incentives need to be implemented thoughtfully because small, seemingly minor holes can be blown wide open and introduce major distortions in the delivery of care. In terms of this whistle blower case, I think we shouldn't dwell on the cows leaving the old barn that has been replaced by one with automatic and secure doors. The old reimbursement system was broken and has been fixed (or at least changed) and I don't think there is much to be gained by dwelling on the previous system's inefficiencies and errors.

So as I see it:
  • Davita administered and wasted dialysis drugs in a way that is uncomfortable, and inefficient but legal.
  • The Government realized the incentives were not aligned with better outcomes and changed the incentives
  • Davita and the other large dialysis organizations have changed their purchasing and administration procedures in response to the new incentives
  • A couple of former employees want to sue Davita for its legal, but opportunistic, drug handling behavior under the old incentives

Transparency: I am a part owner of a dialysis joint venture with Davita and one of my partners, Robert Provenzano, is Davita's VP of Medical Affairs.

Monday, July 25, 2011

Safari's Reader function in Lion

I upgraded to Lion on my MacBook Air last week and I'm using Safari in full screen mode. One of the side-effects of this is that many text based sites are too wide for comfortable reading.

Clicking "Reader" in the address bar (or command-shift-R) drops a shadow across the page and opens an overlay containing the core text of the page minus annoying ads and other visual distractions. Really nice.

Click here

and see this uncluttered clean version of the text

The reader feature was introduced with Safari 5 as part of Snow Leopard but it wasn't until I started living in full-screen mode that the utility of this feature presented itself.

Saturday, July 23, 2011

The problem with numbers, the curse of intermediate end-points

The curse of treating chronic kidney disease is that one is always treating patients to the numbers:
  • Blood pressure. I need to get my patients below 130/80
  • Cholesterol. I need to get their LDL below 100
  • Metabolic bone disease. I need to keep their PTH
    • KDOQI 
      • Stage 3: 35-70
      • Stage 4: 70-110
      • Stage 5: 150-300
    • KDIGO
      • In patients with CKD stages 3–5 not on dialysis, in whom serum PTH is progressively rising and remains persistently above the upper limit of normal for the assay despite correction of modifiable factors, treatment with calcitriol or vitamin D analogs is suggested. (hey KDIGO, thanks for the guideline)
  • Diabetes. I need to keep their Hgb A1c less than 7
  • Anemia. I need to keep their hemoglobin
But these numbers are all intermediate, and from a patient perspective, pretty abstract. Patients don't get PTH angina. Targetting the numbers is a way to shift the odds toward better patient outcomes, to load the dice in the patient's favor. However we cannot allow the numbers to substitute for the real goals of care. I don't really care about your blood pressure, I just want to prevent the heart failure, dementia, kidney failure, stroke and erectile dysfunction that result from the high blood pressure. If you give me a pill that magically improves the blood pressure but doesn't avoid those end-points I'm not interested.

But as the number game has become a larger part of medicine we are getting medications that are pursued and approved only for their ability to fix the numbers. Some have been super successful, statins have repeatedly and reliably shown their ability to reduce events in lockstep with reducing the cholesterol. Lately however, it is feeling like success of the statins to reduce LDL and also reduce cardiovascular events maybe more the exception than the rule.

The recent experience with ESAs and hemoglobin have been beat to death in the nephrology community. See this post for a deep dive. The core issue, is that low hemoglobins are bad for patients, but using ESAs to improve the hemoglobin does not mitigate the risk. And not only does it not mitigate the risk, it appears that the current agents bring with them novel arterial and venous thrombotic risks.

The experience with A1c seems to be playing out using a similar script. Glitazones were approved based on their ability to reduce blood sugars. They effectively lower blood sugar but Rosiglitazone increased the risk of cardiovascular death by 64% and was associated with increased composite outcome of stroke, heart failure and total mortality compared to pioglitazone.

And June 9th pioglitazone was pulled from the shelves in France for increased risk of bladder cancer. A position validated by the FDA on June 15th.

This comes on the heals of three studies in 2008 and 2009 that question the notion of very tight (less than 7%) hemoglobin a1c targets to improve patient outcomes.

In cardiology, following the stunning success of statins and LDL we have a string of failures, Ezetimibe (Zetia/Vytorin) for LDL and niacin/torcetripib for HDL

I often feel the only reason we still treat PTH is that no one has done the study to show that it helps and when we get around to that trial, I'm looking at you Abbott, we will find that it too, has been a waste of money and attention.

Friday, July 8, 2011

Hyaline casts

We just got our microscope serviced. It works great.

- Posted using BlogPress from my iPhone

Thursday, July 7, 2011

Must read article on funding for antibiotic resistance

Maryn McKenna writes about NIH funding for highly resistant bacterial infections. The data comes from a poster by Eli Perecevich (Blog) and ML Scweizer.

The investigators looked at funding into Enterobacter species, MRSA and other resistant staph, C. difficile, Acinetobacter baumanii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Enterococcus faecium as the definition of resistant organism research. In 2009, the NIH spent $398 million. For comparison, in 2007 the NIH spent $1.24 billion dollars on HIV research.

Perecevich and Scweizer then compared the mortality from the different diseases and the relative amount of money spent on them (see graph at right).

Though 95% confidence intervals or P values were not provided, the difference appears significant.

The easy explanation is to blame the politics of AIDS. HIV infection, like breast cancer, is a disease with a well organized and loud constituency and they have labored hard to get funding. Unfortunately that funding comes at the expense of other diseases that may be less visible despite having equivalent impact.

The other cynical answer is to blame capitalism. The fact that HIV treatment is lifelong makes it very profitable for drug companies to focus their research on anti-viral treatment, especially compared to acute bacterial infections that may require only 10 days of treatment. I have secondhand knowledge that in the world venture financed early drug research this is very important, however, these are NIH dollars, which should not be influenced by potential profit.

I think the answer is that the market for drug resistant infection is driven by the availability of good grant requests and interested researchers. For 30 years the best and brightest ID researchers have been going into HIV research, it will take a while to turn that battleship to other areas of interest. Supporting this theory is the fact that research on resistant organisms increased from $180 million to $398 million from 2007 to 2009. So interest and money are being directed to this field but it will take time.

Stupid iPhone tricks: auto-dialing into a phone maze

The phone system in my office allows patients, hospitals and practitioners to leave messages and then calls to alert us about new message. Retrieving the message is a multistep process:

  1. call the main office number
  2. dial a prefix plus my extension
  3. dial my password
  4. enter the code to play back my messages
You can program an iPhone to playback a telephone script to do this. This is a huge aggravation saver.

Create a new contact with an appropriate name

Enter the voicemail number and then tap the bottom left button

This brings up an alternate keypad with 5 buttons

The wait button inserts a semi-colon and the pause botton inserts a comma.
A "wait" will delay sending the next numbers until you tap a button, a pause will delay the next numbers by a second or two. This is what a semicolon looks like when dialing a number:

I use a pause until the phone picks up and then insert a pause after each step so the phone number looks like this:

(313) 886-8787 ; extension , passcode , play-back code

This trick works great.

Wednesday, July 6, 2011

I love the smell of July 1st in the morning

As has been the tradition since 2008, I had the honor of giving the morning report on July 1st for the St John Hospital and Medical Center Internal Medicine Residency Program. July one, openning day of the academic year. The conference room was crackling with the energy of fresh interns and the equally excited second years ready to run their own teams.

Giving the lecture was a lot of fun. There were a lot of insightful questions, some because the questioner is terrified and others to show how smart she is. Nobody looked sleep deprived, so the ratio of deer-in-the-headlights to asleep-at-their-desk was unnaturally high.

The lecture covered three topics:
  1. total body water and how to choose an IV fluid
  2. diuretics
  3. dysnatremia
There is no way I could get through the deck in the 50 minutes of time we had. It probably would take 90 minutes to cover it all. In delivering the talk I focused on the mood of starting this great adventure.

Here are some tips to using this presentation:

The first slide has Munch's Skrik, which I explain translates as July 1st

Slide 4 has my favorite quote about kidney function. Homer Smith essentially uses 150 words to explain the point that the job of the kidneys is not to make urine anymore than the job of a factory is to make smoke.
The lungs serve to maintain the composition of the extra-cellular fluid with respect to oxygen and carbon dioxide, and with this their duty ends. The responsibility for maintaining the composition of this fluid in respect to other constituents devolves on the kidneys. It is no exaggeration to say that the composition of the body fluids is determined not by what the mouth takes in but what the kidneys keep: they are the master chemists of our internal environment. Which, so to speak, they manufacture in reverse by working it over some fifteen times a day. When among other duties, they excrete the ashes of our body fires, or remove from the blood the infinite variety of foreign substances that are constantly being absorbed from our indiscriminate gastrointestinal tracts, these excretory operations are incidental to the major task of keeping our internal environments in the ideal, balanced state.  
Slides 5-9 emphasize that this topic is not a niche topic, the issues of fluids and electrolytes comes up everyday, on every patient.

Slide 11, warn everyone that the unfortunate person who gains 30 kg in this slide is a medicine resident gorging on donuts at morning report.

Slide 18, remind everyone that LR is for surgeons. Deny any knowledge of the reason for this peculiarity. Explain that this is further evidence that they are an alien species unrelated to hard working, honest IM docs.

Slide 27 Explain that the question, "Would you give a drowning man a glass of water?" was taught to me by one of the most foul-mouthed senior residents when I was an intern. I want to show that the lessons learned this year will be the stories you tell interns decades later. Interns will learn more this year than any other year of their life, except their first year of life.

Slide 29 recommend everyone read House of God

Here is the lecture in PDF and Powerpoint

Muddy brown cast via iPhone 4

Using the instructions from the NEJM I captured this muddy brown cast in a patient with acute on chronic acute kidney injury. I love this new tool.

Tuesday, July 5, 2011

The new definition of a rock and a hard place--Updated

The rock would be Amgen with their newest prescribing information for Epogen and Aranesp. The recommendations for dialysis patients can be summarized as:
Specifically, for patients on dialysis, the label advises physicians to initiate ESA therapy when the hemoglobin level is less than 10 g/dL and guides physicians to reduce or interrupt the dose when the hemoglobin approaches or exceeds 11 g/dL.  So target a hemoglobin higher than needed to prevent transfusions and no higher than 11 g/dL.
The hard place would be the federal government whose Quality Improvement Plan (QIP) for dialysis units states:
The intent is to control anemia and maintain optimum hemoglobin levels within the range of 10-12 g/dL (grams per deciliter).  Anemia management will be assessed by two separate measures: 
  1. CMS will assess the percentage of patients whose hemoglobin levels dipped under 10 g/dL.  The program assigns this measure the greatest weight in facility performance calculation, because numbers under 10 g/dL are highly undesirable.  (Weight = 50%)
  2. CMS will assess the percentage of patients whose hemoglobin levels exceeded 12 g/dL. Numbers greater than 12 g/dL could suggest unnecessary or excessive administration of certain drugs.  (Weight = 25%)
There is little air to breathe between 10 and 11 g/dL. Something has got to change and my guess is by the end of the year QIP will be suggesting hemoglobins between 9 and 10.

UPDATE: CMS has proposed new rules that remove the lower limit for hemoglobin as a quality measure. Here is some news coverage and here is the PDF.

I think its crazy to remove the lower hemoglobin limit. When CMS introduced the bundled payment system they turned anemia management from a profit center to a cost center for dialysis units. The Quality Incentive Plan was designed to prevent dialysis units from minimizing costs by denying patients adequate treatment. It seems that with the 2013 proposal, a Machiavellian dialysis unit could eliminate anemia management completely and reap financial rewards without penalty.

This can't be right, at the least CMS should add minimizing transfusions as a quality measure, that would reconcile the prescribing information and the quality goals.

Hat tip to the anonymous first poster.
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